rs797045085
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001277115.2(DNAH11):c.8746C>T(p.Gln2916*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001277115.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DNAH11 | ENST00000409508.8 | c.8746C>T | p.Gln2916* | stop_gained | 53/82 | 5 | NM_001277115.2 | ENSP00000475939.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461658Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 727108
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74334
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 7 Pathogenic:1Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Pathogenic and reported on 06-18-2018 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 01, 2014 | The Gln2916X variant in DNAH11 has not been previously reported in individuals with PCD or in large population studies. This nonsense variant leads to a premature termination codon at position 2916, which is predicted to lead to a truncated or absent protein. Complete loss of DNAH11 function is an established disease mechanism in PCD. In summary, this variant meets our criteria to be classified as pathogenic (http://pcpgm.partners.org/LMM). - |
Primary ciliary dyskinesia Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 09, 2021 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in DNAH11 are known to be pathogenic (PMID: 18022865, 20513915, 22184204). This variant has not been reported in the literature in individuals with DNAH11-related disease. ClinVar contains an entry for this variant (Variation ID: 208572). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln2916*) in the DNAH11 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at